Variant 1-28334525-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017638.3(MED18):c.182A>G(p.Lys61Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MED18
NM_017638.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

MED18 (HGNC:25944): (mediator complex subunit 18) MED18 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

MED18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11012524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MED18	NM_017638.3 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	3/3	ENST00000373842.9	NP_060108.2
MED18	NM_001127350.2 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	3/3		NP_001120822.1
MED18	XM_005245914.5 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	3/3		XP_005245971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MED18	ENST00000373842.9 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	3/3	2	NM_017638.3	ENSP00000362948	P1
MED18	ENST00000398997.2 linkuse as main transcript	c.182A>G	p.Lys61Arg	missense_variant	3/4	5		ENSP00000381963	P1
MED18	ENST00000474683.1 linkuse as main transcript	n.341A>G		non_coding_transcript_exon_variant	3/3	3
MED18	ENST00000479574.5 linkuse as main transcript	n.371A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

The c.182A>G (p.K61R) alteration is located in exon 3 (coding exon 2) of the MED18 gene. This alteration results from a A to G substitution at nucleotide position 182, causing the lysine (K) at amino acid position 61 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

0.00086

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.19

DEOGEN2

Benign

0.033

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

0.0048

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0014

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.37

N;N

MutationTaster

Benign

0.73

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.20

N;N

REVEL

Benign

0.19

Sift

Benign

0.99

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.083

MutPred

0.49

Loss of ubiquitination at K61 (P = 0.0161);Loss of ubiquitination at K61 (P = 0.0161);

MVP

0.18

MPC

0.45

ClinPred

0.49

GERP RS

5.8

Varity_R

0.11

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over